Expression of P-glycoprotein on blood lymphocytes and its role in development of steroid resistance in severe asthma

Abstract

P-glycoprotein (Pgp) is a membrane transporter of hydrophobic molecules providing efflux of xenobiotics from the cytosole outside the cell. In epithelial cells, Pgp is thought to be responsible for resistance to steroids. Severe bronchial asthma (SBA) is a heterogenous disease characterized by resistance to and dependence on steroids. The goal of this study was to assess expression of Pgp on peripheral blood lymphocytes in severe bronchial asthma and to evaluate the role of Pgp in developing the resistance to glucocorticoid therapy (GC). Assessment of Pgp expression revealed difference in response to GC treatment. All the patients were susceptible to GC, however, the time of therapeutic effect appearance and the number of Pgp-immunopositive cells differed significantly. Thus, more prolonged application of GC for reducing clinical manifestations was required in patients with aspirin induced or fatal bronchial asthma. The number of Pgp-immunopositive lymphocytes per one patients was significantly higher in patients with fatal bronchial asthma and in patients with steroid dependent bronchial asthma (6.8 ± 0.1 and 7.2 ± 0.2, respectively) comparing with patients with non stable bronchial asthma being therapeutically resistant (3.2±0.2 and 3.5±0.1, respectively). Thus, our findings suggest possible pathogenic role of Pgp in development of resistance to GC therapy in patients with bronchial asthma. Detection of Pgp expression on peripheral blood lymphocytes would allow optimizing the volume and duration of intensive anti inflammatory therapy and predicting the doses of basic drugs.